U.S. patent number 3,669,880 [Application Number 04/837,714] was granted by the patent office on 1972-06-13 for recirculation dialysate system for use with an artificial kidney machine.
This patent grant is currently assigned to CCI Aerospace Corporation. Invention is credited to Michael A. Greenbaum, Laurence B. Marantz.
United States Patent |
3,669,880 |
Marantz , et al. |
June 13, 1972 |
RECIRCULATION DIALYSATE SYSTEM FOR USE WITH AN ARTIFICIAL KIDNEY
MACHINE
Abstract
A recirculating dialysate system for use with an artificial
kidney in which the total volume of dialysate solution is
controlled. After leaving the artificial kidney, the urea in the
solution is removed in a zirconium phosphate column containing
urease and the other waste products are removed in a carbon column
containing activated carbon and hydrated zirconium oxide. The
solution passes through the dialysate reservoir (or container)
where it was originally introduced and where the level of solution
indicates the amount of fluid removed from the body. Downstream of
the dialysate reservoir, the solution is reconstituted by the
addition of magnesium and calcium (removed in the zirconium
phosphate column) so that these substances will not be removed from
the blood in the kidney. The rate at which water passes from the
blood into the dialysate solution can be controlled by controlling
the pressure of the dialysate solution on the dialysate side of the
kidney membrane, so that sufficient water can be removed to arrive
at water balance in the patient.
Inventors: |
Marantz; Laurence B. (Sherman
Oaks, CA), Greenbaum; Michael A. (Los Angeles, CA) |
Assignee: |
CCI Aerospace Corporation (Van
Nuys, CA)
|
Family
ID: |
25275208 |
Appl.
No.: |
04/837,714 |
Filed: |
June 30, 1969 |
Current U.S.
Class: |
210/632;
210/195.2; 210/321.65; 210/647; 210/648; 210/929; 210/259;
210/321.71 |
Current CPC
Class: |
B01D
61/30 (20130101); A61M 1/1696 (20130101); Y10S
210/929 (20130101) |
Current International
Class: |
A61M
1/16 (20060101); B01d 013/00 (); C02b 001/56 ();
C02b 001/42 () |
Field of
Search: |
;210/321,22,195,29,38,37 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Industrial Research Fellow Report May, Flower, Chemical Engineer,
May 1968, pp. 120-130. .
Large Scale Herodialysis, Leonard, Vol. XI, Trans. Amer. Soc.
Artificial Organs, pp. 25-30, 1965. .
Rosenbaum et al., Trans. Amer. Soc. Artificial Int. Organs, Vol.
XIII, 1967, pp. 183-189. .
Amphlett et al., Synthetic Inorganic Ion Exchange Materials,
Journal Inorg. Nucl. Chem. Vol. 6, 1958 pp. 220-235. .
Blaney et al., Cyclie . . . . Fluid, Chemical Engineering Progress
Symposium, 1968 pp. 112-120..
|
Primary Examiner: Friedman; Reuben
Assistant Examiner: Barnes; Richard
Claims
We claim:
1. In a method of treating a recirculating dialysate solution which
flows past a membrane to pick up impurities from a patient's blood,
comprising the steps of:
treating the dialysate solution with urease to convert urea picked
up by the dialysate solution to ammonium carbonate;
treating the dialysate solution with a zirconium phosphate ion
exchanger to remove ammonium ions from the ammonium carbonate;
treating the dialysate solution with hydrated zirconium oxide to
remove phosphate picked up by the dialysate solution; and
treating the dialysate solution with activated carbon to remove
other waste materials picked up by the dialysate solution.
2. In a method as defined in claim 1, the step of adding calcium
and magnesium to said dialysate solution after treatment with said
zirconium phosphate ion exchanger and before flow past said
membrane.
3. In a method as defined in claim 1, the step of continually
measuring the increase in volume of said dialysate solution to
determine the amount of fluid removed from the patient.
4. In a dialysis apparatus which includes a dialysate recirculating
system for directing a dialysate solution past a membrane to pick
up impurities from a patient's blood.
urease in said recirculating system for converting the urea picked
up by said dialysate solution to ammonium carbonate;
zirconium phosphate ion exchanger in said recirculating system for
removing ammonium ions from the ammonium carbonate;
hydrated zirconium oxide in said recirculating system for removing
phosphate picked up by said dialysate solution, and
activated carbon in said recirculating system for removing other
waste substances picked up by said dialysate solution.
5. In a dialysis apparatus as defined in claim 4 having gauge means
associated with said system for continually measuring the amount of
fluid removed from said patient during dialysis by continually
measuring the increase in solution volume in said system.
6. In a dialysis apparatus as defined in claim 4, a supply of
calcium and magnesium for addition to said system to replace
calcium and magnesium removed by said zirconium phosphate ion
exchanger.
7. In a recirculating dialysate system containing a dialysate
solution for receiving phosphate from an artificial kidney, a
charge of hydrated zirconium oxide in the dialysate solution to
remove phosphate, and means recirculating the dialysate solution
from a phosphate receiving location in the artificial kidney
through said charge and back to said phosphate receiving
location.
8. In a method of treating a dialysate solution which picks up
phosphate at an artificial kidney, the improvement comprising
treating the dialysate solution with hydrated zirconium oxide to
remove the phosphate from the solution, and recirculating the
treated dialysate solution back to the artificial kidney.
9. In a recirculating dialysate system utilizing a dialysate
solution flowing past a membrane for dialysis of a patient:
passage means for directing dialysate solution to said
membrane;
pump means in said passage means for recirculating said dialysate
solution;
means in said passage means for removing impurities from said
dialysate solution added during dialysis;
said removing means comprising urease and zirconium phosphate ion
exchanger for removing urea, hydrated zirconium oxide for removing
phosphate, and activated carbon for removing other toxic
substances;
said zirconium phosphate ion exchanger also removing calcium and
magnesium from the dialysate solution required for dialysis;
means connected with said passage means for reconstituting the
dialysate solution before dialysis with calcium and magnesium
required for dialysis and removed by said zirconium phosphate ion
exchanger.
said reconstituting means comprising a reservoir containing calcium
and magnesium in solution; and means for directing said
reconstituting solution into said dialysate solution.
10. In a recirculating dialysate system as defined in claim 9,
container means connected with said passage means for receiving the
increase in volume of the dialysate solution resulting from fluid
removal from the patient during dialysis; and
means associated with said container means for continually
measuring said increase in volume during dialysis.
11. In a recirculating dialysate system as defined in claim 10,
wherein said measuring means comprises a liquid level gauge.
Description
BACKGROUND OF THE INVENTION
This invention relates to a recirculating dialysate system for use
with an artificial kidney. In order to save a patient with acute
Renal failure or kidney failure which results from loss of kidney
function due to disease or poison or massive shock, it has been the
practice to utilize an artificial kidney until the natural kidneys
can take over and resume functioning. Normally, after a certain
period of dialyzing, the kidneys will commence functioning again.
With chronic Renal failure, the kidneys slowly deteriorate until
they stop functioning altogether or function at such a low level
that they are insufficient for the patient's needs. In most cases,
the kidney deterioration is over a period of years and eventually
becomes acute enough that the patient must have the aid of dialysis
or he will die. At the present time, the amount of funds required
to produce the necessary equipment and support for patients is so
great as to prevent treatment and prevent the death of all
inflicted persons. As a result, a large number of candidates for
dialysis die which could otherwise be saved if there were
facilities available for dialysis.
It has been proposed to add urease to a recirculating dialysate
solution and pass the solution through a zirconium phosphate column
in order to eliminate from the solution the urea which has been
removed from the blood of the patient by the artificial kidney.
This treatment of the dialysate solution is fully disclosed in
copending application Ser. No. 780,417, filed Dec. 2, 1968 now
continuation Ser. Number 92,864 filed Nov. 25, 1970, by the same
inventors.
SUMMARY OF THE INVENTION
In a complete dialysate system it is necessary to consider
components of the blood in addition to urea, and the effect of
dialysis on the blood. The present invention provides a complete
recirculating dialysis system for use with an artificial kidney
which eliminates toxic substances from the dialysate solution and
continually maintains a normal dialysate solution. The dialysate
system can be used with various types of artificial kidneys now
available and the system is small and inexpensive so that it can be
made available to a great number of people who would presently go
without treatment.
It is therefore an object of the present invention to provide a
complete recirculating dialysate system which will remove toxic
substances from the dialysate solution and provide for the
continual maintenance of a normal dialysate solution.
Another object of the invention is to provide a complete
recirculating dialysate system which controls the fluid balance of
the patient so that the required amount of water is removed from
the blood to keep the patient in normal health and water
balance.
Another object of the invention is to provide a small and
inexpensive dialysate system which will be available to the
greatest number of people, the majority of whom must now go without
treatment.
Another object of the invention is to provide a complete
recirculating dialysate system which is self-contained and needs no
outside additions once the dialyzing process is started.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a diagrammatic illustration of the complete recirculating
dialysate system connected with an artificial kidney.
FIG. 2 is an enlarged sectional view of the zirconium phosphate
column; and
FIG. 3 is an enlarged sectional view of the carbon column.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIG. 1, passage 10 connects to the discharge side of
an artificial kidney device 11 and contains a gear pump 12 for
continually recirculating the dialysate solution through the
system. The term "dialysate solution" as used herein refers to the
solution used throughout the dialysis process, whether the solution
is entering or leaving the artificial kidney. A pressure shut-off
switch 13 is connected to output line 14 of the pump through a pipe
15 and serves to stop the pump if the pressure in passage 14
exceeds a predetermined value determined by the pressure which can
be withstood by the components of the system. Passage 14 is also
connected to a cartridge pressure gauge 17 which indicates the
pressure in line 14 upstream of a three-way valve 18 which connects
line 14 to branch line 19 or to the by-pass line 20. The valve 18
can also be placed in a middle position to completely close the
line 14 and stop circulation of the system. Line 19 leads through
the top panel 21 of zirconium phosphate column 22 to an open space
23. At the bottom of the space is a sheet 24 of filter cloth which
covers a layer 25 consisting of mixture of finely divided urease
and diatomaceous earth. The filter cloth keeps the incoming flow
from breaking up the top surface of the layer 25. Immediately below
the layer 25 is a layer 26 of diatomaceous earth which prevents the
urease from moving down in the column. A layer 27 of zirconium
phosphate in fine particle form is located below the layer 26 of
diatomaceous earth. The substance of layers 25 and 26 can be
essentially fine enough to be called dust. Another filter cloth 28
is located between the zirconium phosphate 27 and a flow director
device 29 which directs the dialysate flow to outlet opening 30 in
the bottom plate 31 of the column, connecting with the outlet line
35.
The solution in passage 14 is the standard dialysate solution plus
the waste products (impurities) picked up from the patient by the
artificial kidney 11. These impurities will include urea,
creatinine and uric acid. As the dialysate solution passes through
the layer 25 of urease in column 22, the urea is converted into
ammonia carbonate in accordance with the following
relationship:
In proper operation, substantially all of the urea is converted by
the time the solution enters the zirconium phosphate layer 27. For
instance, the incoming solution in passage 19 can contain 20
milligrams per 100 cc of blood urea nitrogen and will drop to 1 or
2 milligrams as it enters the zirconium phosphate 27. After leaving
the urease, there will be no further change in the urea
concentration. The layer 26 of diatomaceous earth takes out all
colloidal and particle matter which is in the dialysate solution
and prevents its continual circulation in the system.
In flowing through the zirconium phosphate, the ammonium ion is
picked up and is replaced by sodium and hydrogen so that the
ammonium concentration in the outlet line 35 is substantially zero.
This reaction is as follows: 2NH.sub.4 .sup.+ +
Zr(NaPO.sub.4).sub.2 .sup.. H.sub.2 O.fwdarw.Zr(NH.sub.4
PO.sub.4).sub.2 .sup.. H.sub.2 0 + 2Na.sup.+ and
.fwdarw.ZrO(NH.sub.4 NaPO.sub.4).sub.2 + 2H.sup.+Thus, in the
outlet passage 35, the urea concentration has been reduced to 1 or
2 milligrams per 100 cc and the ammonium ion concentration is
substantially zero. It should be noted that the solution in passage
19 and in passage 35 is substantially 99 percent water. It is
understood that the term "zirconium phosphate" utilized throughout
the specification loosely defines zirconium phosphate ion
exchangers, such as the zirconium phosphate sodium form set forth
in the above equation, and it is understood that other forms of
zirconium phosphate ion exchangers can be utilized. The composition
of zirconium phosphate ion exchanger is more fully discussed in
said U.S. Application Ser. No. 780,417 (now No. 92,804). It is
known that zirconium phosphate ion exchanger, not equilibrated with
potassium, strongly absorbs potassium ions and thus, layer 27 will
remove potassium from the dialysate solution. If the potassium form
of zirconium phosphate ion exchanger is utilized in layer 27 the
potassium content of the dialysate can be controlled.
The line 35 connects with carbon cartridge or column 36 which
contains a layer 38 of activated carbon over a layer 39 of hydrated
zirconium oxide. A sheet of filter cloth 40 is located between the
layer 39 and a flow director 41 which has vanes to direct the flow
to outlet line 42. The activated carbon picks up uric acid and
creatinine, as well as other organic waste which are obtained by
the artificial kidney from the patient. The layer 39 of zirconium
oxide picks up phosphate from the solution, the phosphate coming in
part from the patient and in part from the zirconium phosphate.
The by-pass line 20 connects passage 14 with outlet passage 42 when
valve 18 is properly positioned so that line 20 by-passes both the
zirconium phosphate column 22 and the carbon cartridge 36. The
purpose of by-pass line 20 is to permit the complete dialysate
system to fill with liquid after start up since the pump cannot
pump air originally in the line through the column and cartridge.
Once the system is filled with liquid, the valve 18 is turned to
direct the flow through the column 22. The passage 42 leads to
three-way valve 45 which can direct the solution either to the dump
line 46 or to the line 47 leading to the dialysate reservoir
(container) 48.
The dialysate solution is added to the reservoir (container) 48
prior to treatment of the patient by removing the cover 49 and the
level of the solution can be read by the level gauge 50. The air
release port 51 in cover 49 permits air to escape when it is left
open during the treatment. Also, the port can be equipped with a
valve 54 to permit a vacuum or a pressure to be applied within the
container 48 as will be later explained. The original level of the
solution before the start of the dialysis is designated as 52 and
the level will drop to level 53 as the rest of the system fills
with fluid from the reservoir. As water is pulled out of the
patient during the dialysis, the water level will rise again. A
flow meter 56 measures the rate of flow of the recirculating
dialysate solution produced by pump 10 in passage 55.
An infusion flow line 58 connects the line 55 with an infusion
reservoir 59 which contains a dialysate reconstitution solution of
substances, such as magnesium and calcium salt. The line 58
contains infusion pump 62 and infusion meter 61 to control the rate
at which the reconstitution solution is added to the line 55. The
magnesium and calcium are in the normal dialysate solution placed
in reservoir 48 but are removed by the layer 27 of zirconium
phosphate in column 22 and therefore must be returned to the
dialysate solution before it again enters the artificial kidney 11.
The concentration of these substances is controlled in a water
solution in the infusion reservoir 59 and can be controlled to meet
the condition of the patient. In a standard addition, the infusion
flow is at a rate to add 2.5 milliequivalents of calcium and 1.5
milliequivalents of magnesium per liter of dialysate solution. The
reconstituted dialysate solution then passes through heater 64
which brings the temperature of the dialysate solution up to normal
body temperature and this temperature can be measured by the gauge
65 for purposes of control.
An ultra filtration valve 66 is located in passage 55 and consists
of a standard regulating valve which controls the pressure of the
fluid in the dialysate chamber 71 of the artificial kidney. Since
the speed of the pump controls the flow rate, the closing down of
valve 65 will cause the pump 12 to pull a vacuum in chamber 71. The
artificial kidney contains a semi-permeable membrane 73, such as
cellophane, which separates the dialysate side 71 from the blood
chamber 72. Blood from the patient enters chamber 72 from line 77
and leaves the chamber 72 by line 76 so that there is counterflow
between the blood and dialysate solution. The membrane 73 contains
small molecular size holes through which small molecules can pass
and large molecules cannot, the normal critical size being about
10,000 molecular weight. The smaller the molecules are, the faster
they pass through the membrane and the formed elements of the
blood, such as cells (erythrocyte and leucocyte) cannot pass so
that there is no loss of blood cells or protein through the
membrane during dialysis. On the other hand, such molecules as
water, inorganic salts, urea, creatinine, uric acid, amino acids,
glucose, citric acid, etc., will pass through the membrane into the
dialysate solution.
The passage of water through the membrane is controlled almost
entirely by the pressure gradient across the membrane as determined
by the setting of the valve 66. The blood pressure in chamber 77
corresponds with the blood pressure of the patient which is
substantially 100 mm. or 4 psi and the pressure of the dialysate
solution upstream of valve 66 is determined by the pressure in
dialysate reservoir 48. If the air relief port 54 is open, the
pressure will be atmospheric. However, either a vacuum or a
pressure can be imparted to the interior of reservoir 48 and the
air relief valve closed before circulation of the dialysate
solution in order to vary its pressure. A pressure in reservoir 48
would only be utilized when it is desired to stop water removal
from the patient during dialysis and in such case the water gauge
50 would indicate no change in volume. A lower pressure in the
chamber 71 causes fluid to pass from the blood through the membrane
into the dialysate solution at a greater rate. A standard check
valve 73 is located in by-pass line 74 around valve 66 so that
before valve 66 is closed down far enough to cause a pressure drop
sufficient to rupture the kidney membrane, the check valve will
open. The pressure in the dialysate side 71 is continually shown at
the dialysate pressure gauge 75. A higher pressure in the chamber
71 causes fluid to pass from the blood through the membrane into
the dialysate solution at a lower rate. Assuming that the air
release valve 54 is open, it is possible to obtain a pressure on
the opposite side of the membrane ranging from atmospheric to a few
pounds below atmosphere through use of valve 66. It is understood
that the rate of transfer through the membrane can also be
controlled by adjustment of the blood pressure (such as in the
Kolff coil system) rather than adjustment of the dialysate pressure
since it is the pressure gradient that is controlling.
The normal human kidney is responsible for the water balance in the
body and removes such water from the blood as is not lost by other
means. The effectiveness of the artificial kidney in removing water
to maintain the balance is determined by the pressure differential
which is set across the membrane. As the water is taken out of the
blood by the artificial kidney, it is added to the closed dialysate
system and shows up as an addition to the system at the level gauge
50. One advantage of the system is that if the air release hole 51
is closed during the circulation of the dialysis solution, a break
in the kidney membrane cannot remove more blood from the patient
then will fill the remaining space in the reservoir and this amount
of blood removal will not be enough to kill the patient.
In addition to the removal of water, other impurities in the blood,
such as urea, creatinine, uric acid and other unknown toxic
materials, must also be removed and these are removed at a rate
controlled by dialysate flow. The patient has a certain calcium and
magnesium level in his body and if these materials are not in the
dialysate solution when it flows past the artificial kidney 11, the
calcium and magnesium in the patient's blood flows through the
membrane into the dialysate solution and will be subsequently
removed at layer 27. Therefore, the patient would be depleted of
calcium and magnesium if it were not for the continual addition of
these substances to the dialysate solution downstream of layer 27.
It would be possible to reconstitute the blood to compensate for
loss of these substances by injection of these substances directly
into the blood stream at the line leading from the kidney. However,
the injection would require sterile operating conditions and is not
practical or economical.
In summarizing the operation of the system, the dialysate solution
in passage 10 leaving the artificial kidney 11 contains the various
impurities removed by the artificial kidney, such as urea,
creatinine and uric acid and the normal dialysate components,
including the magnesium and calcium that were added at the infusion
line 58. In passing through the zirconium phosphate column 22, all
the urea is removed from the solution along with the magnesium and
calcium that had been added by the infusion line 58. Thereafter, in
passing through the carbon column 36 the impurities uric acid,
creatinine and other organic wastes are removed by the activated
carbon, and the hydrated zirconium oxide removes the phosphate.
Hydrous zirconium oxide is synonymous with hydrated zirconium oxide
and is further described in U.S. Pat. No. 3,332,737 granted July
25, 1967 to Kent A. Kraus. The solution then is reconstituted by
the addition of magnesium and calcium at the infusion line 58 so
that a normal dialysate solution is again available in line 55 for
introduction into the dialysate chamber 71 of the artificial
kidney.
The flow rate of the solution through the kidney is controlled by
pump 12 and the pressure and temperature of the solution at the
artificial kidney can be controlled by the valve 66 and heater 64,
respectively. By varying the pressure of the dialysate solution in
the kidney chamber 71, it is possible to control the rate at which
water is removed at the kidney in order to maintain the water
balance of the patient. The present invention provides a dialysate
system for use with an artificial kidney in which the total volume
of the dialysate solution is strictly controlled and an immediate
measure of the fluid removed from the patient is available. The
total volume of dialysate solution need only be that required to
fill the artificial kidney and system components, which volume
depends upon the volume required to fill the particular type of
artificial kidney employed. In the typical example given in
Application Ser. No. 780,417 (now Ser. No. 92,864) two liters of
dialysate solution circulating at 200 cc per minute effectively
removes urea. Compared with the volume of dialysate solution, the
volume of fluid removed from the patient is sufficient to provide a
reading of volume increase of solution.
The continual infusion into the dialysate solution of magnesium and
calcium assures that these materials will not be removed from the
bloodstream. The use of this reconstitution system makes it
possible to treat each patient according to his varying body
chemistry without the necessity of making up large volumes of
special dialysate for individual patients. Thus, with a standard
reconstitution solution, it is a simple matter to handle all levels
of calcium and magnesium balance simply by varying the rate of
infusion of this reconstitution solution. Patients requiring
addition of special inorganic or organic substances to their bodies
could have this done simply by adding these materials at
appropriate levels to the reconstitution solution.
* * * * *